Tumor secreted ANGPTL2 facilitates recruitment of neutrophils to the lung to promote lung pre-metastatic niche formation and targeting ANGPTL2 signaling affects metastatic disease

Oncotarget Volume 11, Issue 5: The authors determined that tumor-derived ANGPTL2 stimulates lung epithelial cells, which is essential for primary tumor-induced neutrophil recruitment in lung and subsequent pre-metastatic niche formation.

Lastly, they identified that a p63 isoform, Np63, drives a high level of ANGPTL2 secretion and pharmaceutical inhibition of ANGPTL2 signaling by a non-RGD-based integrin-binding peptide diminished metastatic load in lungs likely due to reduction of the lung pre-metastatic niche formation.

Dr. Hakan Cam from the Center for Childhood Cancer and Blood Diseases at Nationwide Children’s Hospital as well as the Department of Pediatrics at The Ohio State University in Columbus Ohio USA said in their Oncotarget paper, “Primary tumors selectively and actively modify potential sites of metastasis, even prior to dissemination“

For instance, neutrophils have been identified as facilitators of breast cancer metastasis and of lung cancer metastasis after UV-induced inflammation through tumor-secreted exosomal RNAs.

Here, the scientists set out to determine how tumor-derived factors might affect the activation of lung epithelial cells in ways that elicit pro-metastatic inflammatory responses and facilitate the formation of the pre-metastatic following the recruitment of neutrophils.

It is also well established that the induction of inflammation-related genes results in the activation of neutrophils and as described above a body of evidence suggesting that the recruitment of neutrophils promotes cancer metastasis.

Collectively, by using spontaneous metastatic models, they investigated whether tumor secreted ANGPTL2 induces inflammation on lung epithelial cells by activating alpha5beta1 receptor and recruiting neutrophils to the pre-metastatic niche.

The Cam Research Team concluded in their Oncotarget article that they investigated whether lung epithelial cells might be essential for primary tumor-induced neutrophil recruitment to lung and the role that these infiltrating cells play in osteosarcoma PMN formation using spontaneous metastatic models.

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Full text – https://doi.org/10.18632/oncotarget.27433

Correspondence to – Hakan Cam – [email protected]

Keywords –
pre-metastatic niche formation,
osteosarcoma,
ANGPTL2,
tumor microenvironment,
neutrophils

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